Development and Validation of Risk Models to Select Ever-Smokers for CT Lung Cancer Screening

Abstract

Importance: The US Preventive Services Task Force (USPSTF) recommends computed tomography (CT) lung cancer screening for ever-smokers aged 55 to 80 years who have smoked at least 30 pack-years with no more than 15 years since quitting. However, selecting ever-smokers for screening using individualized lung cancer risk calculations may be more effective and efficient than current USPSTF recommendations.

Objective: Comparison of modeled outcomes from risk-based CT lung-screening strategies vs USPSTF recommendations.

Design, setting, and participants: Empirical risk models for lung cancer incidence and death in the absence of CT screening using data on ever-smokers from the Prostate, Lung, Colorectal, and Ovarian Cancer Screening Trial (PLCO; 1993-2009) control group. Covariates included age; education; sex; race; smoking intensity, duration, and quit-years; body mass index; family history of lung cancer; and self-reported emphysema. Model validation in the chest radiography groups of the PLCO and the National Lung Screening Trial (NLST; 2002-2009), with additional validation of the death model in the National Health Interview Survey (NHIS; 1997-2001), a representative sample of the United States. Models were applied to US ever-smokers aged 50 to 80 years (NHIS 2010-2012) to estimate outcomes of risk-based selection for CT lung screening, assuming screening for all ever-smokers, yield the percent changes in lung cancer detection and death observed in the NLST.

Exposures: Annual CT lung screening for 3 years beginning at age 50 years.

Main outcomes and measures: For model validity: calibration (number of model-predicted cases divided by number of observed cases [estimated/observed]) and discrimination (area under curve [AUC]). For modeled screening outcomes: estimated number of screen-avertable lung cancer deaths and estimated screening effectiveness (number needed to screen [NNS] to prevent 1 lung cancer death).

Results: Lung cancer incidence and death risk models were well calibrated in PLCO and NLST. The lung cancer death model calibrated and discriminated well for US ever-smokers aged 50 to 80 years (NHIS 1997-2001: estimated/observed = 0.94 [95%CI, 0.84-1.05]; AUC, 0.78 [95%CI, 0.76-0.80]). Under USPSTF recommendations, the models estimated 9.0 million US ever-smokers would qualify for lung cancer screening and 46,488 (95% CI, 43,924-49,053) lung cancer deaths were estimated as screen-avertable over 5 years (estimated NNS, 194 [95% CI, 187-201]). In contrast, risk-based selection screening of the same number of ever-smokers (9.0 million) at highest 5-year lung cancer risk (≥1.9%) was estimated to avert 20% more deaths (55,717 [95% CI, 53,033-58,400]) and was estimated to reduce the estimated NNS by 17% (NNS, 162 [95% CI, 157-166]).

Conclusions and relevance: Among a cohort of US ever-smokers aged 50 to 80 years, application of a risk-based model for CT screening for lung cancer compared with a model based on USPSTF recommendations was estimated to be associated with a greater number of lung cancer deaths prevented over 5 years, along with a lower NNS to prevent 1 lung cancer death.

Figure 1. 5-year modeled outcomes from different risk-based CT lung-cancer screening strategies in US ever-smokers ages 50-80

For example, a lung cancer risk threshold of 0.7% is estimated to screen 49% (21M) of ever-smokers ages 50-80, prevent 90% (74,021) of preventable deaths over 5 years, screen 287 people to prevent 1 death, result in 185 false-positive CT screens per prevented death, and diagnose 0.94 extra lung cancers per prevented death. The asterisks on the figure denote the data markers for current USPSTF and CMS recommendations but the only axes that apply to these two points are the estimated number and % preventable, and the estimated # and % screened. USPSTF recommendations are estimated to screen 9.0 million (21%) of ever-smokers age 50-80, might prevent 46,488 lung-cancer deaths over 5 years (57% of the preventable deaths), screen 194 people to prevent one death, result in 133 false-positive CT screens per prevented death, and diagnose 0.93 extra lung cancers per prevented death. CMS recommendations are estimated to screen 8.7 million (20%) of ever-smokers age 50-80, might prevent 41,559 lung-cancer deaths over 5 years (51% of the preventable deaths), screen 208 people to prevent one death, result in 142 false-positive CT screens per prevented death and diagnose 0.94 extra lung cancers per prevented death. Strategies below the curve, such as USPSTF and CMS recommendations, are estimating as having less screening effectiveness than risk-based strategies. USPSTF recommendations are estimated as having more screening effectiveness than CMS recommendations because CMS recommendations exclude older smokers (ages 78-80), who can have higher risks of lung cancer.